Experimental animal research strongly implicates prenatal stress in the long-term behavioral/emotional, cognitive, and neuroendocrine disturbance in offspring in a manner suggesting a programming mechanism. Recently reported data suggest that a parallel association may exist for prenatal anxiety in humans. The potential implications of these findings for understanding and preventing mental health problems in children and adults are both obvious and substantial. Basic questions remain, however, about the persistence of effects in humans, the mechanisms underlying the association, and the role of postnatal environmental experiences and genetic factors in accounting for individual variation. This proposal addresses these questions in the context of a unique multidisciplinary prospective, longitudinal study of a large community sample that has been continuously followed since early pregnancy. The study proposes to conduct in-person assessments of approximately 8,000 14 year-olds who have been followed since birth and for whom exposure to prenatal maternal anxiety and postnatal psychosocial adversity has been well-characterized. Data on psychopathology and HPA axis functioning at age 14 will be predicted from the interplay between previously collected data on maternal anxiety in pregnancy, specific psychosocial risks, and polymorphisms for the glucocorticoid receptor genes. The current study would provide a state-of-the-science investigation of prenatal anxiety that will have substantial impact on developmental theory and public health, and build on and extend research into the genetic bases of individual differences in stress vulnerability and psychopathology Specific aims of this research are to a) examine the long-term effects of prenatal anxiety on dimensional and diagnostic measures of psychopathology in early adolescence; b) assess the role of the HPA axis underlying the links between prenatal anxiety on adolescent psychopathology and stress vulnerability; c) test competing hypotheses concerning the processes by which prenatal anxiety has direct, mediated or moderated effects on adolescent psychopathology; and d) test the hypothesis that the effects of prenatal anxiety/stress on behavioral/emotional problems in early adolescence are moderated by genetic risk. [unreadable] [unreadable]